Sclerotherapy for the intraoral ranula with bleomycin: technical considerations and preliminary experience.

Ranula is a mucous cyst that occurs in the sublingual gland (SLG) in the floor of the mouth. It can be classified into two types based on origins: One is the the lesser sublingual gland (LSLG) in the anterior segment and the Rivini duct, which is connected to it, and the other is the greater sublingual gland (GSLG) in the posterior segment. Because of the anatomical characteristics, surgical resection of the cysts carries the risk of damaging adjacent tissues and has a high recurrence rate. Intralesional injection of sclerotherapy may be a better alternative treatment. We summarized 65 cases of ranula treated with intralesional injections of bleomycin(BML). According to the origin of the ranula, 60 cases were from the LSLG and the Rivini duct, and 5 cases were from the GSLG. The results showed that 60 cases of ranula from LSLG and Rivini ducts were 100% cured during the follow-up period. The median number of injections for all patients was 1.16. All 5 cases of ranula from the GSLG did not wholly recover. This study confirmed that BLM intralesional injection is a safe and effective treatment modality for cysts from LSLG or the ducts of Rivini rather than GSLG. Therefore, before treatment, it is necessary to determine the type and origin of the cyst by characterizing its morphology to ensure the effectiveness of the treatment.

Characterizing Chemotherapy/Radiotherapy-Induced Genome Chaos in Hodgkin's Lymphoma Patients Using M-FISH.

Hodgkin lymphoma (HL) is one of the most common lymphomas, with an incidence of 3 per 100,000 persons. Current treatment uses a cocktail of genotoxic agents, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), along with or without radiotherapy. This treatment regimen has proved to be efficient in killing cancer cells, resulting in HL patients having a survival rate of >90% cancer-free survival at five years. However, this therapy does not have a specific cell target, and it can induce damage in the genome of non-cancerous cells. Previous studies have shown that HL survivors often exhibit karyotypes characterized by complex chromosomal abnormalities that are difficult to analyze by conventional banding. Multicolor fluorescence in situ hybridization (M-FISH) is a powerful tool to analyze complex karyotypes; we used M-FISH to investigate the presence of chromosomal damage in peripheral blood lymphocytes from five healthy individuals and five HL patients before, during, and one year after anti-cancer treatment. Our results show that this anti-cancer treatment-induced genomic chaos that persists in the hematopoietic stem cells from HL patients one year after finishing therapy. This chromosomal instability may play a role in the occurrence of second primary cancers that are observed in 10% of HL survivors. This chapter will describe a protocol for utilizing M-FISH to study treatment-induced genome chaos in Hodgkin's lymphoma (HL) patients, following a brief discussion.

Vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma.

Vanishing bile duct syndrome is an uncommon condition characterised by the progressive loss and disappearance of bile ducts. It is an acquired form of cholestatic liver disease presenting with hepatic ductopenia (loss of >50% bile ducts in the portal areas). We present a case of vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma who was treated with standard-of-care chemotherapy-doxorubicin, bleomycin, vinblastine and dacarbazine (along with brief administration of rituximab), which led to complete response and normalisation of liver function.

Nongestational ovarian choriocarcinoma with bilateral teratoma: A rare case report and literature review.

INTRODUCTION: Trophoblastic neoplasms are often associated with pregnancy, and nongestational trophoblastic neoplasms are extremely rare. Nongestational ovarian choriocarcinoma (NGCO) is a highly aggressive germ cell-derived tumor frequently presenting with early hematogenous metastasis. PATIENT CONCERNS: Herein, we report a case of a 28-year-old unmarried woman with regular menstruation who experienced vaginal bleeding 1 week after her last menstrual cycle. Doppler ultrasound revealed bilateral adnexal masses and elevated serum human chorionic gonadotropin (hCG) levels. The patient was initially misdiagnosed as presenting an ectopic pregnancy. DIAGNOSIS: The final pathology confirmed an International Federation of Gynecology and Obstetrics stage IA NGCO with bilateral mature teratoma of the ovary. This is an extraordinary instance of ovarian choriocarcinoma which emerged without any prior gestation, and the patient's lack of a history of pregnancy made the diagnosis ignored. INTERVENTIONS: After initial surgery and 1 cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, a laparoscopic fertility-preserving comprehensive staging surgery was performed. Two cycles of chemotherapy with BEP were administered as supplemental therapy postsurgery, and leuprorelin was administered to protect ovarian function. OUTCOMES: Menstruation resumed 4 months after chemotherapy completion, and tumor indicators were within the normal range. No signs of recurrence were observed at the 36-month follow-up. CONCLUSION: NGCO should be considered if a female patient exhibits irregular vaginal bleeding and masses in the adnexal area. The present case and our literature review also highlighted that fertility-sparing surgery and multidrug chemotherapy are effective methods for treating NGCO.

Real-life study on the use of response adapted therapy in patients with Hodgkin Lymphoma: Results from a multicenter experience.

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment-naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real-life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real-life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty-one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p = 0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow-up of 72 months, the 5-year progression-free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5-year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real-world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response-adapted strategy which however did not translate into a difference in patient outcomes.

Transcatheter Arterial Embolization with Bleomycin-Lipiodol of Hepatic Hemangiomas: Safety, Efficacy and Predictors of Response.

PURPOSE: To evaluate the safety, efficacy and predictors of response of transcatheter arterial embolization (TAE) to treat hepatic hemangiomas (HHs). MATERIALS AND METHODS: A retrospective analysis was conducted of consecutive HH patients who received TAE with bleomycin-Lipiodol emulsion and gelatin sponge particles at three institutions from January 2014 to January 2021. TAE effectiveness was defined as more than 50% reduction of tumor volume. The effectiveness, safety, and CT changes of hemangiomas after TAE were assessed. Factors affecting TAE efficacy on tumor size were analyzed with logistic regression analysis. RESULTS: A total of 102 patients with 109 HHs were included. After treatment, both the tumor diameter and volume were significantly reduced from 8.5 ± 3.9 to 5.9 ± 3.8 cm (P < 0.001) and 412.6 ± 742.3 cm3 to 102.0 ± 232.7 cm3 (P < 0.001), respectively. TAE effectiveness was achieved in 80.7% (88/109) of hemangiomas, which was characterized by progressive reduction in tumor volume over time with Lipiodol retention. Atypical enhancement pattern (tiny enhancing dots in the hepatic arterial and portal venous phase) (p = 0.001) and central arterioportal shunt (APS) (p = 0.002) associated with the tumor were independent predictors of TAE ineffectiveness. Postembolization syndrome and transient increase in liver enzymes were common without severe complications and death. CONCLUSION: TAE was safe and effective in reducing HH size. Lesion enhancement pattern and APS type were associated with TAE efficacy on tumor shrinkage. LEVEL OF EVIDENCE: Level 3, non-controlled retrospective cohort study.

Transarterial embolization with bleomycin-lipiodol emulsion: a successful minimal invasive approach for giant liver hemangioma.

Hemangiomas are most common benign liver tumor. Most patients have an excellent prognosis because of the small size and benign nature of tumor. On some occasions, giant liver hemangioma may cause symptoms and significant challenges due to its complication. We report a case of giant liver hemangioma treated with minimal invasive approach by transarterial embolization (TAE). Following three TAE sessions over a specific timeframe, the patient was successfully managed, addressing that TAE may be a useful alternative to hepatic surgery in such cases.

Multiple External Cervical Resorption Lesions in Patient with Graft versus Host Disease Treated with Systemic Bleomycin: A Case Report.

The phenomenon of multiple external cervical root resorption (ECRR) lesions in a single patient is rare but may have a link with the chemotherapeutic agent bleomycin. This case details an adult male with multiple ECRR lesions that developed following chemotherapy. His treatment regimen for Hodgkin's lymphoma included the chemotherapeutic antibiotic bleomycin, which has previously been linked with development of multiple ECRR lesions. The patient developed graft versus host disease following an allogeneic stem cell transplant, which could have a significant role in the development and promotion of the ECRR lesions. In total, 8 teeth developed ECRR, and all the known causative factors were excluded when examined. To our knowledge, this is only the second reported case in the literature to link bleomycin to multiple ECRR lesions. This case report aims to bring the reader's attention to the fact that multiple cervical resorption lesions can develop simultaneously. These lesions can be difficult to diagnose and treat and are often misdiagnosed as caries. Finally, the reader should consider the possible role of bleomycin and graft versus host disease in development of multiple lesions of ECRR.

Efficacy of Bleomycin-Lauromacrogol Foam in Pediatric Macrocystic Lymphatic Malformations With and Without Intracapsular Hemorrhage.

BACKGROUND: Sclerotherapy is purportedly less effective in patients with hemorrhagic than with non-hemorrhagic lymphatic malformations (LMs). We aimed to compare the efficacy of bleomycin-lauromacrogol foam (BLF) sclerotherapy in the treatment of macrocystic LMs with and without intralesional hemorrhage. METHODS: Fifty-five children with macrocystic LMs admitted to the Pediatric Surgery Department were retrospectively included. The patients were allocated into a hemorrhage group (23 cases) or a non-hemorrhage group (32 cases) based on the occurrence of an intracapsular hemorrhage. The diagnosis was confirmed by physical examination, color ultrasound, magnetic resonance imaging, and puncture findings. BLF was injected into the capsule after draining the cystic fluid under color ultrasound guidance. Patients whose lesions were unchanged or showed minor change after 1 month were treated again using the same method. Changes in lesion size and the number of treatments were recorded. Effectiveness was classified as excellent (volume reduction ≥90%), good (50%≤volume reduction<90%), or poor (volume reduction <50%). RESULTS: In the hemorrhage group, 17, 6, and 0 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 100%. In the non-hemorrhage group, 23, 7, and 2 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 93.8%. There was no significant difference in efficacy rate between groups (P = 0.767). CONCLUSIONS: BLF is an effective and safe treatment for macrocystic LMs with bleeding. The results were similar in patients with and without bleeding. LEVEL OF EVIDENCE: Treatment, Level III.

Comparative Efficacy of Drug Interventions for Keloids: A Network Meta-analysis.

BACKGROUND: Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological problems. The optimal treatment for keloids is yet to be standardized. Intralesional injection, which is simple and nontraumatic, is one of the most commonly used treatment modalities for these lesions. In this study, we compared 5 different drugs (intralesional injections) for the treatment of keloids in terms of efficacy. METHODS: We systemically searched relevant studies on PubMed, EMBASE, and Cochrane Library. Randomized clinical trials on the safety and efficacy of triamcinolone acetonide (TAC), 5-fluorouracil (5-FU), botulinum toxin A (BTA), verapamil, and bleomycin were included in this study. RESULTS: This network meta-analysis included a total of 1114 patients from 20 randomized controlled trials. Botulinum toxin A alone and TAC plus 5-FU exhibited significantly better efficacy than did 5-FU, TAC, and verapamil. No significant difference in efficacy between BTA alone and TAC combined with 5-FU was observed. No significant differences were noted in the adverse event rate between BTA, TAC plus 5-FU, 5-FU, and TAC. Furthermore, we performed surface under the cumulative ranking curve analyses to predict the rank of each intervention (by efficacy and adverse event rate). The predicted ranking by efficacy was as follows: TAC plus 5-FU, BTA, bleomycin, TAC, 5-FU, and verapamil; the predicted ranking by adverse events was as follows: TAC, 5-FU, TAC plus 5-FU, and BTA. Funnel plot analysis revealed no publication bias. CONCLUSIONS: Botulinum toxin A and TAC plus 5-FU appear to have outstanding therapeutic efficacy for keloids. The rate of adverse events was similar among BTA, TAC, 5-FU, and TAC plus 5-FU. Nonetheless, additional reviews of rigorous, large-scale randomized controlled trials are warranted for further validation of our findings.

Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations.

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.

Additive value of single intralesional bleomycin injection to propranolol in the management of proliferative infantile hemangioma.

BACKGROUND: /Objective: We aimed to evaluate whether additional intralesional bleomycin injections benefit children with proliferative infantile hemangiomas (IHs). METHODS: In this retrospective case-control study, we examined the medical records of 216 infants who were followed up for proliferative IH. Patients in group 1 were treated with propranolol orally at 2 mg/kg/day. Group 2 was treated with oral propranolol combined with intralesional bleomycin injections. RESULTS: We retrospectively reviewed 95 and 121 patients in groups 1 and 2, respectively. No significant differences were observed between both groups regarding visiting age, sex, lesion thickness, or risk site. The overall cure rates in groups 1 and 2 were 77.89% (74/95) and 84.30% (102/121), respectively. The overall distribution of the length of cure significantly differed between both groups (P = 0.035). From the survival analysis (P = 0.026), the median survival time was 198 days (95% confidence interval (CI) 174.46-221.54) for group 1 and 139 days (95% CI 114.58-163.42) for group 2. The effect of treatment modality (hazard ratio (HR) = 1.41, P = 0.031) and risk site on survival time (HR = .54, P < 0.001) was significant. CONCLUSION: No significant differences were observed in the resolution of proliferative IH; however, intralesional bleomycin injection with systemic propranolol for proliferative IH treatment may provide a more rapid resolution.

Tislelizumab monotherapy in patients with previously untreated early-stage classical Hodgkin lymphoma: a real-world study.

The anti-PD-1 antibodies have been reported to show a striking effect in relapsed and refractory(R/R) classical Hodgkin lymphoma (cHL), however, there is still limited real-world data assessing the role of anti-PD-1 antibody monotherapy in early-stage cHL. In this retrospective analysis, we reported the effectiveness and safety of tislelizumab monotherapy in the first-line therapy of early-stage cHL. Twenty-three consecutive patients (10 males and 13 females) with previously untreated stage I A-II B cHL were included. At interim evaluation after 2 doses of tislelizumab monotherapy, 11 of 23 patients (47.8%) achieved complete response (CR). At the end of tislelizumab monotherapy (EOTM), objective response was observed in 22 of 23 patients (95.7%), with CR in 16 patients (69.6%). Among six patients with PR-EOTM, two patients underwent 4 cycles of ABVD chemotherapy and one patient underwent 4 cycles of tislelizumab plus AVD. One patient who developed progressive disease (PD) after 4 doses of tislelizumab subsequently underwent 4 cycles of ABVD chemotherapy. Except for four patients with CR-EOTM, consolidative radiotherapy was given to 19 patients. All patients obtained CR at the end of all treatments. With a median follow-up time of 21.3 months (range, 6.9-32.7 months), the estimated 2-year PFS rate and 2-year OS rate were 95.65% and 100%, respectively. Except for grade 3 lymphocyte count decreased, no other grade 3/4 TRAE was observed. In addition, no serious AE was reported. Our preliminary data observed that tislelizumab monotherapy was safe and highly effective in previously untreated early-stage cHL.

Needle-free electronically-controlled jet injector treatment with bleomycin and lidocaine is effective and well-tolerated in patients with recalcitrant keloids.

OBJECTIVES: The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. METHODS: This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. RESULTS: Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. CONCLUSIONS: EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.

Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction.

OBJECTIVES: To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). METHODS: prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n=13), papillary thyroid carcinoma (n=4), adenoid cystic carcinoma of parotid gland (n=1) or malignant melanoma (n=37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. RESULTS: Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p= 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p= 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p= 0.86). CONCLUSIONS: Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. LEVEL OF EVIDENCE: III.